US2025003979A1PendingUtilityA1
Metabolomic profiles for prediction of functional neurological outcome or death following severe traumatic brain injury
Est. expiryJul 9, 2041(~15 yrs left)· nominal 20-yr term from priority
G01N 2800/56G01N 2800/2871G01N 2570/00G01N 33/6806G01N 33/66G01N 33/5308G01R 33/465G01N 2800/52G01N 33/6896G01N 33/6848
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Claims
Abstract
The present disclosure provides a method of determining a likelihood of a favorable or unfavorable outcome, such as death or a Glasgow Outcome Scale Extended (GOSE) score≤4, in a subject having severe traumatic brain injury (sTBI). The method involves quantitative assessment of multiple metabolites shortly after the injury, such as on day 1 and/or day 4 for changes indicative of outcome. Quantitative mass spectrometry (MS) or proton (1H) nuclear magnetic resonance spectroscopy (NMR) may be used to assess multiple metabolites within a single blood sample for comparison with a control.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of determining a likelihood of an unfavourable outcome in a subject having a severe traumatic brain injury (sTBI), comprising:
obtaining a sample from a subject at day 1 and/or day 4 post sTBI, measuring an amount of a plurality of metabolites in the sample, and comparing levels of the plurality of metabolites in the sample with a control; wherein an outcome of the comparing step is an increase or decrease in quantity of said plurality of metabolites in the sample relative to the control, and wherein unfavourable outcome is determined as likely when: in the day 1 sample, at least two, or at least 5, of the following metabolites of the plurality of metabolites are changed relative to the control: C3:1, LYSOC17:0, LYSOC18:0, LYSOC16:0, C18:2, LYSOC18:1, C14, C18:1, C18, C16, tyrosine, homocysteine, C3, CO, C4, ornithine, LYSOC14:0, SM 16:1 OH, LYSOC20:3, LYSOC28:1, phenylalanine, glutamine, PC ae 36:0, histidine, SM 20:2, isoleucine, citrulline, methionine-sulfoxide, asymmetric dimethylarginine, C5OH, C10:2, acetyl-ornithine, C9, methionine-sulfoxide, spermine, serotonin, serine, trans-hydroxyproline, succinate, gluconate, acetone, lactate, glycerol, betaine, choline, alanine, and 3-hyroxyisovalerate; and/or in the day 4 sample, at least two, or at least 5, of the following metabolites of the plurality of metabolites are changed relative to the control: valine, N-acetylaspartate, tyrosine, lysine, dimethylsulfone, taurine, gluconate, hypoxanthine, beta-alanine, C3OH, glutamic acid, LYSOC18:0, PC36:0AA, C18:2, C3:1, C3, ornithine, CO, SM 16:1 OH, LYSOC14:0, LYSOC20:3, homocysteine, C16:1, glutamine, beta-hydroxybutyric acid, uric acid, serotonin, C9, PC ae 36:0, methionine-sulfoxide, serine, a-dimethylarginine, spermine, and trans-hydroxyproline; wherein the unfavourable outcome comprises a Glasgow Outcome Scale Extended (GOSE) score≤4 from 3 months to 12 months post sTBI.
2 . The method of claim 1 , wherein said likelihood of said unfavorable outcome is determined for three months following the sTBI.
3 . The method of claim 1 , wherein said likelihood of said unfavorable outcome is determined for twelve months following the sTBI.
4 . The method of claim 1 , wherein said likelihood of said unfavorable outcome is determined from a Day 1 sample, with an increase or decrease in the at least two, or the at least 5, metabolites as per Tables 35A, 35B, 37A, or 37B:
Lyso PC 17:0
Up
Lyso PC 18:0
Up
C3:1
Up
Lyso PC 16:0
Up
Lyso PC 18:1
Up
C18:2
Up
C14
Up
C18
Up
C18:1
Up
C16
Up
C14:2
Up
Tyrosine
Down
Asparagine
Down
PC ae 36:0
Down
C16:2
Down
Phenylalanine
Down
C16:1
Down
Glutamine
Down
SM 20:2
Down
PC aa 32:2
Down
Isoleucine
Down
Citrulline
Down
Histidine
Down
Glutamate
Down
Methionine-Sulfoxide
Down
Asymmetric
Down
dimethylargine
LYSOC17:0
Up
LYSOC18:0
Up
LYSOC16:0
Up
C18:2
Up
C14
Up
C18:1
Up
C18
Up
C16
Up
Glutamine
Down
Histidine
Down
SM 20:2
Down
Methionine-sulfoxide
Down
Asymmetric
Down
dimethylarginine
C5OH
Down
Homocysteine
Up
C3
Up
C0
Up
C4
Up
Ornithine
Up
LYSOC14:0
Up
SM 16:1 OH
Up
LYSOC20:3
Up
LYSOC28:1
Up
C10:2
Down
Acetyl-ornithine
Down
C9
Down
Adimethylarginine
Down
Methionine-sulfoxide
Down
Spermine
Down
PC ae 36:0
Down
Citrulline
Down
Serotonin
Down
Serine
Down
trans-Hydroxyproline
Down
C3
Up
Ornithine
Up
C0
Up
SM 16:1 OH
Up
LYSOC14:0
Up
LYSOC20:3
Up
Homocysteine
Up
Serotonin
Down
C9
Down
PC ae 36:0
Down
Methionine-sulfoxide
Down
Serine
Down
Adimethylarginine
Down
Spermine
Down
trans-Hydroxyproline
Down
5 . The method of claim 1 , wherein said likelihood of said unfavorable outcome is determined from a Day 4 sample, with an increase or decrease in the at least two, or the at least 5, metabolites as per Tables 36A, 36B, 38A, or 38B:
C3OH
Up
Glutamic acid
Up
LYSOC18:0
Up
Ornithine
Up
PC aa3 6:0
Up
C18:2
Up
alpha-Aminoadipic acid
Up
Indole acetic acid
Up
C3:1
Up
PC aa 40:2
Down
C16:1
Down
Serine
Down
Glutamine
Down
beta-Hydroxybutyric acid
Down
Uric acid
Down
C3OH
Up
Glutamic acid
Up
LYSOC18:0
Up
Ornithine
Up
PC36:0AA
Up
C18:2
Up
C3:1
Up
C16:1
Down
Glutamine
Down
beta-Hydroxybutyric acid
Down
Uric acid
Down
C6
Up
C3 OH
Up
C18:1 OH
Up
Tryptophan
Up
C3:1
Up
Tyrosine
Up
Creatinine
Up
LysoPC 14:0
Up
Alanine
Up
C16
Up
C2
Down
C14
Down
Beta-hydroxy butyric
Down
Spermine
Down
Betaine
Down
C14:2
Down
Aspartic acid
Down
C18
Down
C6
Up
C3 OH
Up
Tryptophan
Up
C3:1
Up
Tyrosine
Up
Creatinine
Up
LysoPC 14:0
Up
C14
Down
Beta-hydroxy butyric
Down
Betaine
Down
C14:2
Down
Aspartic acid
Down
C18
Down
6 . A method of determining a likelihood of mortality within three months in a subject having a severe traumatic brain injury (sTBI), comprising:
obtaining a sample from a subject at day 1 and/or day 4 post sTBI, measuring an amount of a plurality of metabolites in the sample, and comparing levels of the plurality of metabolites in the sample with a control, wherein an outcome of the comparing step is an increase or decrease in quantity of said plurality of metabolites in the sample relative to the control, and wherein increased likelihood of mortality is determined when: in the day 1 sample, at least two, or at least 5, of the following metabolites of the plurality of metabolites are changed relative to the control: C3:1, PC aa 38:0, glucose, C16:2, leucine, C10:2, valine, isoleucine, histidine, C16OH, glutamine, betaine, 3-hydroxyisovalerate, citrate, and lactate; and/or in the day 4 sample, at least two, or at least 5, of the following metabolites of the plurality of metabolites are changed relative to the control: isobutyrate, valine, lysine, 2-aminobutyrate, hypoxanthine, taurine, gluconate, betaine, alpha-ketoglutaric acid, C16:2OH, hippuric acid, indole acetic acid, PC aa 36:0, ornithine, PC aa 38:0, alpha-aminoadipic acid, tryptophan, leucine, C12:1, C6, glutamine, and LysoPC 26:0.
7 . The method of claim 6 , wherein said likelihood of mortality is determined from a Day 1 sample, with increase or decrease in said at least 2, or said at least 5, of the plurality of metabolites as per Tables 43A, 43B, 45A, or 45B:
C3:1
Up
PC aa 38:0
Up
Glucose
Up
PC ae 40:6
Up
C10:1
Up
C14:1
Up
C14
Up
C10
Up
C16:2
Up
C8
Up
C12
Up
Citrulline
Down
C10:2
Down
Leucine
Down
Valine
Down
Isoleucine
Down
Histidine
Down
C16 OH
Down
Glutamine
Down
C3:1
Up
PC aa 38:0
Up
Glucose
Up
C16:2
Up
Leucine
Down
C10:2
Down
Valine
Down
Isoleucine
Down
Histidine
Down
C16 OH
Down
Glutamine
Down
Glucose
Up
Betaine
Up
3-Hydroxyisovalerate
Up
Citrate
Up
O-Phosphocholine
Up
Dimethyl Sulfone
Up
Formate
Up
Fumarte
Up
2-Oxglutarate
Up
Pyruvate
Up
Lactate
Down
Valine
Down
Isoleucine
Down
Leucine
Down
Diemthylamine
Down
Glutamine
Down
Histidine
Down
Glucose
Up
Betaine
Up
3-Hydroxyisovalerate
Up
Citrate
Up
Lactate
Down
8 . The method of claim 6 , wherein said likelihood of mortality is determined from a Day 4 sample, with an increase or decrease in said at least 2, or said at least 5, of the plurality of metabolites as per Tables 44A, 44B, 46A, 46B, or 46C:
Indole acetic acid
Up
Alpha-Ketglutaric acid
Up
Hippric acid
Up
C16:2 OH
Up
Ornithine
Up
PC aa 36:0
Up
C3
Up
Threonine
Up
Alpha-Aminoadipic acid
Up
PC aa 38:0
Up
Tyrosine
Up
Valine
Up
Tryptophan
Up
C2
Down
C8
Down
C12:1
Down
Betaine
Down
C6
Down
Glutamine
Down
Taurine
Down
LysoPC 26:0
Down
Alpha-Ketoglutaric acid
Up
C16:2 OH
Up
Hippuric acid
Up
Indole acetic acid
Up
PC aa 36:0
Up
Ornithine
Up
PC aa 38:0
Up
Alpha-Aminoadipic acid
Up
Tryptophan
Up
Valine
Down
Leucine
Down
C12:1
Down
C6
Down
Glutamine
Down
LysoPC 26:0
Down
Taurine
Down
Isobutyrate
Up
Creatine
Up
Creatinine
Up
Valine
Up
Lysine
Up
Asparagine
Up
Leucine
Up
Tyrosine
Up
2-Aminobutyrate
Up
4-Hydroxybutyrate
Down
Methionine
Down
Urea
Down
Hypoxanthine
Down
Taurine
Down
Gluconate
Down
Betaine
Down
Isobutyrate
Up
Valine
Up
Lysine
Up
2-Aminobutyrate
Up
Hypoxanthine
Down
Taurine
Down
Gluconate
Down
Betaine
Down
Valine
Up
Lysine
Up
Taurine
Down
Gluconate
Down
Betaine
Down.
9 . A method of determining a likelihood of an outcome in a subject having a severe traumatic brain injury (sTBI) or suspected of having an sTBI, comprising:
obtaining a sample from a subject at day 1 or day 4 post-sTBI, measuring an amount of a plurality of metabolites in the sample, and comparing levels of the plurality of metabolites in the sample with a control, wherein an outcome of the comparing step is an increase or decrease in quantity of said plurality of metabolites in the sample, (i) wherein the likelihood of unfavourable outcome at 3 months is determined:
(a1) in a day 1 sample assessed by quantitative MS, wherein at least 2, at least 5, or at least 10 metabolites of said plurality of metabolites are increased or decreased relative to the control as indicated of the 26 metabolites in Table 35A:
Lyso PC 17:0
Up
Lyso PC 18:0
Up
C3:1
Up
Lyso PC 16:0
Up
Lyso PC 18:1
Up
C18:2
Up
C14
Up
C18
Up
C18:1
Up
C16
Up
C14:2
Up
Tyrosine
Down
Asparagine
Down
PC ae 36:0
Down
C16:2
Down
Phenylalanine
Down
C16:1
Down
Glutamine
Down
SM 20:2
Down
PC aa 32:2
Down
Isoleucine
Down
Citrulline
Down
Histidine
Down
Glutamate
Down
Methionine-Sulfoxide
Down
Asymmetric
Down
dimethylargine
or of the 13 metabolites in Table 35B:
LYSOC17:0
Up
LYSOC18:0
Up
LYSOC16:0
Up
C18:2
Up
C14
Up
C18:1
Up
C18
Up
C16
Up
Glutamine
Down
Histidine
Down
SM 20:2
Down
Methionine-sulfoxide
Down
Asymmetric dimethylarginine
Down;
or
(a2) in a day 4 sample assessed by MS/MS, wherein at least 2, at least 5, or at least 10 metabolites of said plurality of metabolites are increased or decreased relative to the control as indicated, of the 15 metabolites in Table 36A:
C3OH
Up
Glutamic acid
Up
LYSOC18:0
Up
Ornithine
Up
PC aa3 6:0
Up
C18:2
Up
alpha-Aminoadipic acid
Up
Indole acetic acid
Up
C3:1
Up
PC aa 40:2
Down
C16:1
Down
Serine
Down
Glutamine
Down
beta-Hydroxybutyric acid
Down
Uric acid
Down,
or of the 11 metabolites in Table 36B:
C3OH
Up
Glutamic acid
Up
LYSOC18:0
Up
Ornithine
Up
PC36:0AA
Up
C18:2
Up
C3:1
Up
C16:1
Down
Glutamine
Down
beta-Hydroxybutyric acid
Down
Uric acid
Down;
or
(b1) in a day 1 sample assessed by proton (1H) nuclear magnetic resonance spectroscopy (NMR), wherein at least 2, at least 5, or at least 10 metabolites of said plurality of metabolites are increased or decreased relative to the control as indicated, of the 12 metabolites in Table 39A:
Ornithine
Up
Glucose
Up
Acetone
Up
Lactate
Up
Glycerol
Up
Betaine
Up
Choline
Up
Serine
Up
Glycine
Up
Formate
Up
Isoleucine
Down
Dimethylamine
Down,
or at least 5 of the 6 metabolites in Table 39B:
Ornithine
Up
Acetone
Up
Lactate
Up
Glycerol
Up
Betaine
Up
Choline
Up;
or
(b2) in a day 4 sample assessed by NMR, wherein at least 2, or at least 5 metabolites of said plurality of metabolites are increased or decreased relative to the control as indicated, of the 9 metabolites in Table 40A:
Valine
Up
N-Acetylaspartate
Up
Tyrosine
Up
Lysine
Up
Histidine
Up
Dimethyl Sulfone
Up
Pyruvate
Down
Taurine
Down
Gluoconate
Down,
or of the 6 metabolites in Table 40B:
Valine
Up
N-Acetylaspartate
Up
Tyrosine
Up
Lysine
Up
Taurine
Down
Gluconate
Down;
or
(ii) wherein the likelihood of unfavourable outcome at 12 months is determined:
(c1) in a day 1 sample, assessed by QUANTITATIVE MS, wherein at least 2, at least 5, or at least 10 metabolites of said plurality of metabolites are increased or decreased relative to the control as indicated, of the 21 metabolites in Table 37A:
C5OH
Down
Homocysteine
Up
C3
Up
C0
Up
C4
Up
Ornithine
Up
LYSOC14:0
Up
SM 16:1 OH
Up
LYSOC20:3
Up
LYSOC28:1
Up
C10:2
Down
Acetyl-ornithine
Down
C9
Down
Adimethylarginine
Down
Methionine-sulfoxide
Down
Spermine
Down
PC ae 36:0
Down
Citrulline
Down
Serotonin
Down
Serine
Down
trans-Hydroxyproline
Down
or of the 15 metabolites in Table 37B:
C3
Up
Ornithine
Up
C0
Up
SM 16:1 OH
Up
LYSOC14:0
Up
LYSOC20:3
Up
Homocysteine
Up
Serotonin
Down
C9
Down
PC ae 36:0
Down
Methionine-sulfoxide
Down
Serine
Down
Adimethylarginine
Down
Spermine
Down
trans-Hydroxyproline
Down;
or
(c2) in a day 4 sample, assessed by quantitative MS, wherein at least 2, at least 5, or at least 10 metabolites of said plurality of metabolites are increased or decreased relative to the control as indicated, of the 18 metabolites in Table 38A:
C6
Up
C3 OH
Up
C18:1 OH
Up
Tryptophan
Up
C3:1
Up
Tyrosine
Up
Creatinine
Up
LysoPC 14:0
Up
Alanine
Up
C16
Up
C2
Down
C14
Down
Beta-hydroxy butyric
Down
Spermine
Down
Betaine
Down
C14:2
Down
Aspartic acid
Down
C18
Down
or of the 13 metabolites in Table 38B:
C6
Up
C3 OH
Up
Tryptophan
Up
C3:1
Up
Tyrosine
Up
Creatinine
Up
LysoPC 14:0
Up
C14
Down
Beta-hydroxy butyric
Down
Betaine
Down
C14:2
Down
Aspartic acid
Down
C18
Down;
or
(d1) in a day 1 sample assessed by NMR, wherein at least 2, or at least 5 metabolites of said plurality of metabolites are increased or decreased relative to the control as indicated, of the 8 metabolites in Table 41A:
Ornithine
Up
Valine
Up
Succinate
Up
Leucine
Up
Gluconate
Up
Alanine
Up
Mannose
Down
3-Hyroxyisovalerate
Down,
or at least 4 of the 5 metabolites in Table 41B:
Ornithine
Up
Succinate
Up
Gluconate
Up
Alanine
Down
3-Hyroxyisovalerate
Down;
or
(d2) in a day 4 sample assessed by NMR, wherein at least 2, or at least 5 metabolites of said plurality of metabolites are increased or decreased relative to the control as indicated, of the 9 metabolites in Table 42A:
Dimethyl sulfone
Up
Tyrosine
Up
Hisitidine
Up
Valine
Up
Leucine
Up
Taurine
Up
Hypoxanthine
Down
Isopropanol
Down
Beta-alanine
Down,
or of the 5 metabolites in Table 42B:
Dimethyl sulfone
Up
Tyrosine
Up
Valine
Up
Hypoxanthine
Down
Beta-alanine
Down;
or
(iii) wherein the likelihood of mortality outcome is determined:
(e1) in a day 1 sample, assessed by quantitative MS, wherein at least 2, at least 5, or at least 10 metabolites of said plurality of metabolites are increased or decreased relative to the control as indicated, of the 19 metabolites in Table 43A:
C3:1
Up
PC aa 38:0
Up
Glucose
Up
PC ae 40:6
Up
C10:1
Up
C14:1
Up
C14
Up
C10
Up
C16:2
Up
C8
Up
C12
Up
Citrulline
Down
C10:2
Down
Leucine
Down
Valine
Down
Isoleucine
Down
Histidine
Down
C16 OH
Down
Glutamine
Down
or of the 11 metabolites in Table 43B;
C3:1
Up
PC aa 38:0
Up
Glucose
Up
C16:2
Up
Leucine
Down
C10:2
Down
Valine
Down
Isoleucine
Down
Histidine
Down
C16 OH
Down
Glutamine
Down;
or
(e2) in a day 4 sample, assessed by quantitative MS, wherein at least 2, at least 5, or at least 10 metabolites of said plurality of metabolites are increased or decreased relative to the control as indicated, of the 22 metabolites in Table 44A:
Indole acetic acid
Up
Alpha-Ketglutaric acid
Up
Hippric acid
Up
C16:2 OH
Up
Ornithine
Up
PC aa 36:0
Up
C3
Up
Threonine
Up
Alpha-Aminoadipic acid
Up
PC aa 38:0
Up
Tyrosine
Up
Valine
Up
Tryptophan
Up
C2
Down
C8
Down
C12:1
Down
Betaine
Down
C6
Down
Glutamine
Down
Taurine
Down
LysoPC 26:0
Down,
or of the 16 metabolites in Table 44B:
Alpha-Ketoglutaric acid
Up
C16:2 OH
Up
Hippuric acid
Up
Indole acetic acid
Up
PC aa 36:0
Up
Ornithine
Up
PC aa 38:0
Up
Alpha-Aminoadipic acid
Up
Tryptophan
Up
Valine
Down
Leucine
Down
C12:1
Down
C6
Down
Glutamine
Down
LysoPC 26:0
Down
Taurine
Down;
or
(f1) in a day 1 sample, assessed by NMR, wherein at least 2, at least 5, or at least 10 metabolites of said plurality of metabolites are increased or decreased relative to the control as indicated, of the 17 metabolites in Table 45A:
Glucose
Up
Betaine
Up
3-Hydroxyisovalerate
Up
Citrate
Up
O-Phosphocholine
Up
Dimethyl Sulfone
Up
Formate
Up
Fumarte
Up
2-Oxglutarate
Up
Pyruvate
Up
Lactate
Down
Valine
Down
Isoleucine
Down
Leucine
Down
Diemthylamine
Down
Glutamine
Down
Histidine
Down,
or at least 4 of the 5 metabolites in Table 45B:
Glucose
Up
Betaine
Up
3-Hydroxyisovalerate
Up
Citrate
Up
Lactate
Down;
or
(f2) in a day 4 sample, assessed by NMR, wherein at least 2, or at least 5 metabolites of said plurality of metabolites are increased or decreased relative to the control as indicated, of the 16 metabolites in Table 46A:
Isobutyrate
Up
Creatine
Up
Creatinine
Up
Valine
Up
Lysine
Up
Asparagine
Up
Leucine
Up
Tyrosine
Up
2-Aminobutyrate
Up
4-Hydroxybutyrate
Down
Methionine
Down
Urea
Down
Hypoxanthine
Down
Taurine
Down
Gluconate
Down
Betaine
Down,
of the 8 metabolites in Table 46B:
Isobutyrate
Up
Valine
Up
Lysine
Up
2-Aminobutyrate
Up
Hypoxanthine
Down
Taurine
Down
Gluconate
Down
Betaine
Down,
or at least 2 or 4 of the 5 metabolites in Table 46C:
Valine
Up
Lysine
Up
Taurine
Down
Gluconate
Down
Betaine
Down.
10 . The method of claim 9 , wherein said likelihood of said unfavorable outcome is predicted for three months following the sTBI.
11 . The method of claim 9 , wherein said likelihood of said unfavorable outcome is predicted for twelve months following the sTBI.
12 . The method of claim 9 , wherein said likelihood of mortality is predicted.
13 . The method of any one of claims 1 to 12 , wherein sample is a serum sample.
14 . The method of any one of claims 1 to 13 , wherein the control is a value determined from individuals with an orthopedic injury (OI) without head injury, or from a cohort of individuals with sTBI having a favorable outcome.
15 . The method of any one of claims 1 to 14 , wherein said amount of said plurality of metabolites are assessed by NMR.
16 . The method of any one of claims 1 to 14 , wherein said amount of said plurality of metabolites are assessed by quantitative MS.
17 . The method of any one of claims 1 to 16 , wherein said sample is obtained at day 1 following the sTBI.
18 . The method of any one of claims 1 to 16 , wherein said sample is obtained at day 4 following the sTBI.
19 . The method of any one of claims 1 to 12 , wherein said sample is obtained at day 1 and day 4 following the sTBI.
20 . The method of claim 9 , wherein the likelihood of unfavourable outcome at 3 months is determined by assessing the increase or decrease in the following metabolites:
(a1) in a day 1 sample, assessed by quantitative MS wherein the metabolites are increased or decreased as indicated in Table 35A or Table 35B; (a2) in a day 4 sample, assessed by quantitative MS wherein the metabolites are increased or decreased as indicated in Table 36A or Table 36B; (b1) in a day 1 sample, assessed by NMR wherein the metabolites are increased or decreased as indicated in Table 39A or Table 39B; or (b2) in a day 4 sample, assessed by NMR wherein the metabolites are increased or decreased as indicated in Table 40A or Table 40B.
21 . The method of claim 9 , wherein the likelihood of unfavourable outcome at 12 months is determined by assessing the increase or decrease in the following metabolites:
(c1) in a day 1 sample, assessed by quantitative MS wherein the metabolites are increased or decreased as indicated in Table 37A or Table 37B; (c2) in a day 4 sample, assessed by quantitative MS wherein the metabolites are increased or decreased as indicated in Table 38A or Table 38B; (d1) in a day 1 sample, assessed by NMR wherein the metabolites are increased or decreased as indicated in Table 41A or Table 41B; or (d2) in a day 4 sample, assessed by NMR wherein the metabolites are increased or decreased as indicated in Table 42A or Table 42B.
22 . The method of claim 9 , wherein the likelihood of mortality outcome at 3 months is determined by assessing the increase or decrease in the following metabolites:
(e1) in a day 1 sample, assessed by quantitative MS wherein the metabolites are increased or decreased as indicated in Table 43A or Table 43B; (e2) in a day 4 sample, assessed by quantitative MS wherein the metabolites are increased or decreased as indicated in Table 44A or Table 44B; (f1) in a day 1 sample, assessed by NMR wherein the metabolites are increased or decreased as indicated in Table 45A or Table 45B; or (f2) in a day 4 sample, assessed by NMR wherein the metabolites are increased or decreased as indicated in Table 46A, Table 46B, or Table 46C.
23 . The method of claim 9 , wherein the likelihood of mortality outcome at 3 months is determined by assessing the increase or decrease in metabolites:
(e1) in a day 1 sample, assessed by quantitative MS wherein the metabolites are increased or decreased as indicated in Table 43B; (e2) in a day 4 sample, assessed by quantitative MS wherein the metabolites are increased or decreased as indicated in Table 44B; (f1) in a day 1 sample, assessed by NMR wherein the metabolites are increased or decreased as indicated in Table 45B; or (f2) in a day 4 sample, assessed by NMR wherein the metabolites are increased or decreased as indicated in Table 46C.
24 . A kit for predicting outcome of a traumatic brain injury in a subject comprising:
reagents for detecting the metabolites listed in any one of Tables 35A, 35B, 36A, 36B, 37A, 37B, 38A, 38B, 39A, 39B, 40A, 40B, 41A, 41B, 42A, 42B, 43A, 43B, 44A, 44B, 45A, 45B, 46A, 46B, or 46C, and instructions for conducting the method of any one of claims 1 to 23 .Cited by (0)
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